title: Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents.
abstract: An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in vitro and in vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be the most active; exhibited an IC₅₀ value of 0.2 μM and >180 fold selectivity. The hydrochloride salt of (26g) showed 84.26 ± 4.44 percent inhibition at 50 mg/kg × 5 days (twice daily, oral route) dose in L. donovani/hamster model. The efficacy was well correlated with the PK data observed which indicating that the compound is well distributed.
authors.affiliation: Advinus Therapeutics Pvt. Ltd., Bangalore 560 058, India.
authors.forename: Vadiraj S
authors.initials: VS
authors.lastname: Gopinath
authors.forename: Jakir
authors.initials: J
authors.lastname: Pinjari
authors.forename: Ravindra T
authors.initials: RT
authors.lastname: Dere
authors.forename: Aditya
authors.initials: A
authors.lastname: Verma
authors.forename: Preeti
authors.initials: P
authors.lastname: Vishwakarma
authors.forename: Rahul
authors.initials: R
authors.lastname: Shivahare
authors.forename: Manjunath
authors.initials: M
authors.lastname: Moger
authors.forename: Palusa Sanath
authors.initials: PS
authors.lastname: Kumar Goud
authors.forename: Vikram
authors.initials: V
authors.lastname: Ramanathan
authors.forename: Prosenjit
authors.initials: P
authors.lastname: Bose
authors.forename: M V S
authors.initials: MV
authors.lastname: Rao
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Puri
authors.forename: Delphine
authors.initials: D
authors.lastname: Launay
authors.forename: Denis
authors.initials: D
authors.lastname: Martin
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D015195:Drug Design; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008297:Male; D051379:Mice; D021261:Parasitic Sensitivity Tests; D011804:Quinolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D011804:Quinolines
keywords: 2-Substituted quinolines; Antileishmanial activity; Liver microsomes; Luciferase assay; Metabolic stability